Innovate Life Technology MGI Tech Co., Ltd.

Microbial Detection
Total Solution
MGI sequencing platform
for pathogen fast identification
 Innovate Life Technology 01
MGI Tech Co., Ltd.

About us MGI Tech Co., Ltd. (MGI), a subsidiary of BGI Group, is committed to enabling effec-
tive and affordable healthcare solutions for all. Based on its proprietary technology,
MGI produces sequencing devices, equipment, consumables, and reagents to
support life science research, medicine and healthcare.
MGI’s multi-omics platforms include genetic sequencing, mass spectrometry, and
medical imaging. Providing real-time, comprehensive, life-long solutions, its mission
is to develop and promote advanced life science tools for future healthcare.

Timeline of
MGI Microbial Solutions

MGI founded BGISEQ-50 entering Chinese CDC

2015.11 2016.04.13 2016.11 2017.04

BGISEQ-500 launched BGISEQ-50 launched

globally at ICG-10 globally at ICG-11
 02 Microbiological Detection Total Solution

Table of Contents Overview 03

Applications 05

Our Advantages 06

MGI sequencing 07
MGI analysis software 08

Our Solution 09

Hands-on operation 11
Automatic operation solution 12

Our Report 13

Case Study 14

MGISEQ-2000, MGISEQ-200 and MGIFLP, the world’s

first Modular NGS Workstation launched at ICG-12

2017.09 2017.11 2018.02

MGI and CURETIS (a German company) achieved Memorandum about “Cooperation of China-Brazil Infectious Diseases
strategic cooperation to open a new era of genetic and Prevention Research Center” jointedly signed by Brazil FIOCRUZ
diagnosis of infectious diseases foundation, Shenzhen Third People's Hospital, MGI, Institute of
Microbiology, Chinese Academy of Sciences and so on
 03

Overview

How to identify the pathogen that leads

to infectious disease?

Identification of pathogens is essential in the treatment of patients

with infectious diseases. Currently, the predominant techniques rely
on conventional microbiology approaches. However, traditional
methods often fail to identify mixed-pathogens in complex clinical
samples, making the diagnosis and treatment of infection more
challenging. Therefore, a rapid and precise pathogen detection
approach is important to understand and treat the infection.

The challenge of applying NGS technology to

pathogen detection

High-throughput sequencing technology empowers the large-scale

pathogen screening by generating large amounts of genomics data.
However, the tremendous amount of raw information requires a
well-built database and efficient analysis tools to support accurate
identification.

MGI sequencing technology for pathogen detection

MGI has developed a high-throughput sequencing platform integrated

with a pathogen detection system. This innovative technology can
perform fast, accurate and comprehensive pathogen screening for
clinical diagnosis. Moreover, MGI provides varies hardware devices
and compatible reagent kits for the system to support an extensive
range of pathogen testing.
04 Microbiological Detection Total Solution

Traditional pathogen detection methods

Culture-based method TOF-MS (Time-of-flight mass spectrometry)

Laborious, time-consuming. Need clonal isolates.

Not suitable for unculturable pathogens.
Few positive results.

Immunoassay PCR screening

Sensitivity and specificity issues. Can only detect known pathogens and
prone to assay specific limitations.

Each method has its limitation and can only detect known pathogens.

MGI sequencing approach

Sample
(without culture)

Sample High-throughput sequencing

preparation Data analysis

Step 1:Nucleotide extraction Step 2:library preparation Step 3:high-throughput sequencing Step 4:data analysis

Microbial identification report

24 hours from sample to result

Fast, accurate and comprehensive pathogen detection

 05

Applications
MGI NGS platform supports massive screening on unknown
pathogens in human or animal infection and allows accurate
diagnosis and treatment. Its diverse applications are listed below:

Animal health Agriculture Travel health

Animal science Public Prevention and control of

and medicine health human and animal diseases

Food safety Public healthcare Precision medicine

The MGI NGS platform allows detection of

Unculturable pathogens Pathogens without time-consuming culture Co-infection

Infection of a rare or new pathogen strain Hard-to-detect dysbacteriosis

As a highly-integrated sequencing system, MGI sequencing platform provides quick and reliable data for
precise pathogen detection.
06

Our Advantages

Microbial detection total solution of MGI can perform massive unknown pathogen screening with rapid and
precise identification that accurately diagnose and aid treatment decisions. Importantly, our cutting-edge
NGS platform benefits routine clinical microbiological diagnosis.

Independent platforms No need for preliminary test

Fully-automated sample preparation system, No culture needed. Solutions for a wide variety of
high-throughput sequencing platform and environmental or clinical samples (human or
various compatible reagent kits. animal blood, respiratory tract fluid, cerebrospinal
fluid and intestine).

Up-to-date microbial database On-board analysis system

A comprehensive database of 20,000 microbial Reliable data analysis at both nucleic acid and
genomics enabling massive screening at one protein levels.
time.

Streamlined workflow

24 hours from sample to result-all in one stop.

 07

MGI's microbial detection total solution is

based on the data generated by
independent high-throughput sequencing
platform, automated sample preparation
system, self-developed compatible
reagents, and self-developed rapid
identification system for pathogen
infection, which could realize fast,
accurate and comprehensive microbial
detection.

Independently developed platforms

MGI’s fully-integrated sequencing system enables NGS technology to support the
real-time diagnosis of infectious diseases.

Genetic Sequencer

Product Information

Product model MGISEQ-200 MGISEQ-2000

Product feature Efficient Flexible

Flow cell FCS FCS FCL

Lane/Chip 1 LANE 2 LANE 4 LANE

Output Model Medium Medium High

Maximum Output/RUN 60 GB 165 GB 1080 GB

Average Effective Signal Point ~ 300 M ~ 550 M ~1800 M

Minimum Read Length SE50 SE50

Maximum Read Length PE100 PE150

Product Certification CB,CE, cTUVus and EAC

Microbial Detection Throughput up to 16;up to 32;16-96

08 Microbiological Detection Total Solution

Automated sample preparation system

MGISP-100 automated sample preparation system integrates nucleic acid
extraction and library preparation into one instrument, providing a fast, stable and
highly efficient workflow.

Nucleic Acid Extraction Hybridization Capture and PCR

Enzymatic Reactions

Magnetic Bead Purification Library Pooling DNB Preparation Certification: CE, CB, cTUVus
and Fragment Selection

Independently Developed Analysis Software

Pathogen Fast Identification System

MGI has developed PFI (Pathogen Fast Identification) software with a
database containing the genetic information of nearly 20,000 microbes.
The integrated system can quickly generate analyses of microbial genome
information.

Product features

Simple workflow Species coverage Comprehensive analysis

The instrument has automatic
analysis software to launch data
analysis and FASTQ files which are
compatible for secondary analysis.
In addition to human reference genome
sequence, the system collects information
about common animal reference sequences
such as pig, goat, sheep, mice, rat, carp,
goose, chicken, duck, cow, cat, dog and
rabbit. The feature enables comprehensive
analysis to identify host species.
MGI sequencers eliminate high background
or noisy sequencing signal to generate
highly accurate pathogen identification
using RNA transcriptome and DNA genomic
sequencing.
 Innovate Life Technology 09
MGI Tech Co., Ltd.

Product introduction
MGI-developed pathogen fast identification system integrates a supported server, database for data analysis,
and ZLIMS software for more than data management.

Database
Microbial classification Species Genus
The pathogen fast identification
Bacteria 3878 1058
system collects approximately 20,000
microbial genomic sequences (if the Archaea 470 124

species has multiple reference Viruses 7334 729

genomes, the information will also be
Fungi 7738 1929
included) in the database which
Parasites 551 310
supports rapid and precise detection.

Workflow

Raw data
Data
quality Remove the reads with low quality, adaptors and “N”
control

Remove RNA (Host & microbial transcriptome) DNA (Host & microbial genome)
the host
Remove rRNA and host genome Remove rRNA and host genome

Non-host data

Alignment with database and classification

Data
alignment Basic information Results of identification

QC result 1. Summary of RNA/DNA

classification
Interactive “Genus & species” list
2. Identification of RNA/DNA pie chart of identification
RNA vs DNA result

ZLIMS ZLIMS, a MGI laboratory information management software, supports tracking sequencing
runs, data generation and management. The pathogen fast identification system integrates
onboard ZLIMS to monitor run progress of sample collection, library preparation, sequencing
and launch automated data analysis.

Manage the details of each experiment step

Manage the priority of each workflow
Effectively schedule all resources
Monitor sequencing quality and instrument information in real-time
Trace the whole workflow of experimental data
Support all kinds of biological information analysis process and report
 10

Our Solution

MGI microbial detection total solution does not require sample culture and preliminary tests. Additionally, it can
identify microorganisms in environmental or clinical samples at one stop.

1 2 3 4 5
Sample Collection Nucleic Acid Extraction Sequencing Bioinformatics
Report
And Accession And Library Preparation And Base-calling Analysis

blood, throat swab

collection, phlegm, RNA RNA
bronchoalveolar metatranscriptome
lavage fluid, MGISEQ-200 Pathogen Fast
cerebrospinal fluid, DNA DNA Identification System
feces and different cfDNA metagenomics MGISEQ-2000
tissues

High-throughput Bioinformatics
sample collection Nucleic acid extraction Library construction sequencing analysis Report

ATCGATCGATCG ATCGATCGATCG
GACGCTTGAACA Pathogen sequences
to be tested
TTACAACTGTAG
CCGATCGGACGT CCGATCGGACGT
ATGGTTCAATCC Standand pathogen
sequences in datobase

The MGI pathogen fast identification system is highly versatile, providing solutions for a broad range of
detection with the customized panel at one stop.
 11

Hands-on
operation

Flexible and Comprehensive

Offers the pathogen fast identification of various DNA/RNA sample from blood, throat swab collection,
phlegm, bronchoalveolar lavage fluid, cerebrospinal fluid, feces and different tissues.

Sample source
Plasma/Blood/ throat swab collection, phlegm, bronchoalveolar
Step 1 lavage fluid, cerebrospinal fluid, feces and different tissues

Nucleic acid extraction Extraction kit

MagPure Circulating DNA kitB
MGIEasy Magnetic beads Microbiome DNA extraction Kit
MGIEasy Magnetic beads Viral DNA/RNA extraction Kit

Step 2 Nucleic acid source

cfDNA or 150-250bp fragmented DNA
Library construction gDNA (mechanical fragmentation)
gDNA (enzymatic fragmentation)
Total RNA

Library construction kit

MGIEasy Cell-free DNA Library Prep Set
MGIEasy Universal DNA Library Prep Set
MGIEasy FS DNA Library Prep Set
MGIEasy RNA Library Prep Set

Step 3
High-throughput
sequencing
MGISEQ-2000 MGISEQ-200

High-throughput sequencing
MGISEQ-2000RS High-throughput Sequencing Set
MGISEQ-200RS High-throughput Sequencing Set

Step 4
Bioinformatics analysis

Analysis software
Pathogen Fast Identification System
Analysis server
of bioinformatics

Hands on time Automatic time

12

Automatic
operation solution

Simple and Efficient

Offers the pathogen fast identification of various DNA/RNA sample from blood, throat swab collection,
phlegm, bronchoalveolar lavage fluid, cerebrospinal fluid, feces and different tissues. Fully-automated system
provides a fast, convenient and efficient user experience for pathogen detection.

Step 1
Sample source
Nucleic acid extraction Plasma/Blood/ throat swab collection, phlegm, bronchoalveolar
lavage fluid, cerebrospinal fluid, feces and different tissues

Extraction kit
MagPure Circulating DNA kitB
MGIEasy Magnetic beads Microbiome DNA extraction Kit
MGIEasy Magnetic beads Viral DNA/RNA extraction Kit
Step 2 Nucleic acid source
Library construction cfDNA or 150-250bp fragmented DNA
gDNA (enzymatic fragmentation)
Total RNA

Library construction kit

MGIEasy Cell-free DNA Library Prep Set
MGIEasy FS DNA Library Prep Set
MGIEasy RNA Library Prep Set MGISP-100

Step 3
High-throughput
sequencing
MGISEQ-2000 MGISEQ-200

High-throughput sequencing
MGISEQ-2000RS High-throughput Sequencing Set
MGISEQ-200RS High-throughput Sequencing Set

Step 4
Bioinformatics analysis

Analysis software
Pathogen Fast Identification System
Analysis server
of bioinformatics

Hands on time Automatic time

 13

Our Report

The MGI sequencer automatically generates pathogen detection report in a short time
including two main sections：

General information
The system automatically removes low-quality
host/rRNA sequence in raw data and calculates
clean reads and qualified data.

Identification result
The system initially analyzes DNA/RNA level by
comparing the sample sequencing information to
the database of bacterial, viral, archaeal, fungal
and parasite genomes. Subsequently it gener-
ates a pathogen identification report shown as
the Venn diagram. The report includes both DNA
and RNA identification result and comparison of
DNA versus RNA result.

2.1 Summary 2.2 DNA identification

2.3 RNA identification 2.4 RNA vs DNA

14

Case Study

The microbial detection total solution is to understand the diversity within samples by sequencing all nucleotides
of both host and microbes. This method does not require preliminary knowledge of pathogenic microbial
genomes and as such, can identify unknown pathogens in infectious disease. Importantly, the unique identifica-
tion technique supports developing strategies to control and prevent human and animal infectious diseases.

Case 1 Identification of a novel or variant pathogen strain

Overview A 4-year-old boy was hospitalized with clinical presentations of

hand-foot-and-mouth disease including fever and vesicular exanthema on
his hands, feet, oral mucosa, and anus for 1 week. The qRT-PCR results
revealed that the causative agent was HEV instead of EV71 or CVA16. To
further verify the pathogen, a stool sample was collected from the patient
for metagenomic sequencing.

Analysis server of bioinformatics

The stool specimen was collected for Pathogen Fast Identification with
Solution
automated RNA isolation, library preparation and high-throughput sequencing.

Result Ten non-overlapping contigs were assembled after high-throughput

sequencing and verified by mapping to the genomes of three pathogens:
human coxsackievirusA24, enterovirus96, and human poliovirus 1.
Primers were used to amplify the sequences and analsyis suggested that
all the contigs belonged to a consensus sequence of new strain EV-96. It
is the first time that metagenomic sequencing has been used to identify
an EV-96 strain as the cause of HFMD.

Paper A novel Enterovirus 96 circulating in China

causes hand, foot, and mouth disease
published on Virus Genes on February 7th, 2017
 Innovate Life Technology 15
MGI Tech Co., Ltd.

Case 2 Identification of co-infections

A 26-year-old woman developed a mild respiratory illness on Jan.

Overview
28, 2017, but symptoms progressed to recurrent fever, cough, chills,
expectoration, slight hemoptysis, muscle and joint pain in the
following days. On February 3, the patient was hospitalized due to worsening symptoms of cyanotic lips, fever of
39.3 °C, heart rate of 144 beats/ min and diagnosed with severe pneumonia with ARDS. She was treated with
antibiotics and antiviral therapies and then discharged on February 17. Blood and respiratory secretions were
collected during her hospitalization for pathogen testing. The screening results from bacteria and fungi
culture-based test, G-test and GM-test were all negative. In addition, HIV, HBV, influenza viruses, SARS-CoV,
MERS- CoV and other coronaviruses were negative by ELISA and/or (RT-)PCR assays.

Pulmonary secretions from the patient were

Solution
collected on the first day of hospitalization and
analyzed using metagenomic sequencing to
determine the cause of infection. Analysis server of bioinformatics

Equine infectious anemia virus

Two respiratory viruses, HRV and HBoV
Result HHV-5
Enterovirus A
were identified in high abundance using (150)
Torque teno virus 10
WU Polyomavirus
sequencing and confirmed by specific
(RT-)qPCR assays and a report generated Bocavirus
(197)
to diagnose acute co-infection of HBoV1 Rhinovirus C
(1309)
and HRV-C.
FaGmV
(283)
In this case, metagenomic sequencing
showed a significant advantage in
detection of the causative agents of Total=2166 Figure B Viral reads distribution.
severe illness over traditional methods
such as culture, ELISA, PCR, etc.
because prior knowledge was not
assumed or required.

Paper Metagenomic analysis identified

co-infection with human rhinovirus
C and bocavirus 1 in an adult
suffering from severe pneumonia
Published on Journal of Infection in
March 2018
16

Case 3 Diagnosis of rare pathogen

On August 20, 2018, A 42-year-old man was hospitalized after

Overview
presenting with symptoms of severe headache, fever of 38.4 °C,
and elevated CSF leukocyte and protein levels. 24 hours post-pre-
sentation, the patient spoke incoherently, had breathing difficulties,
became comatose and was subsequently transferred to ICU.
Further examination by CT scan showed hydrocephalus and brain edema. Four days later, a
culture from cerebrospinal fluid samples showed negative results for bacteria and fungi,
therefore, to identify the pathogen, the sample was further analyzed using high-throughput
sequencing on August 31. Results were reported to clinicians 2 days later.

The cerebrospinal fluid sample collected from the

Solution
patient was analyzed on the MGI sequencing platform
using the Pathogen Fast Identification workflow.
Analysis server of bioinformatics

Interestingly the results revealed a low level (0.0266%) of sequencing

Result
reads that identified as Naegleria fowleri, a rare amebic pathogen that
can cause primary amebic menigioencephalitis (PAM).

Naegleria fowleri(N=65,658 Reads)

human: 92.7916%
Naegleria: 0.0266%

Read Depth
Bacteria: 0.005%
Fungi: 0.0165%
Viruses: 0%
Others: 3.7076%
Unclassified: 3.4527%

coverage(%):0.264363 mean_depth:15
Windows(1000dp) along Naegleria flowleri Genome

Naegleria: 0.3689%
Bacteria: 0.0689%
Fungi: 0.2291%
Viruses: 1e-04%
Others: 51.4348%
Unclassified: 47.8982%

Total Reads Distribution Reads Distribution

without Huamm Host

PAM caused by Naegleria fowleri infection is extremely rare in China but almost always fatal. The patient went to the Songkran Festival
prior to the onset of illness and may have come into contact with sewage. In this case, traditional methods failed to detect the pathogen,
however, the MGI high-throughput sequencing platform successfully identified the rare pathogen.
 Innovate Life Technology 17
MGI Tech Co., Ltd.

Case 4 Public health issue

A 45-year-old male returning to China from Angola showed symptoms of Rift Valley fever including fever
Overview
(38.8 °C), chills, headache, arthralgia, anorexia and enervation on July 13 and was hospitalized for
treatment. BGI assisted the Entry-exit Inspection and Quarantine of China to obtain a whole genome
sequence of Rift Valley fever virus from the individual using NGS technology. As a result, BGI helped
identify, quarantine and treat the individual and prevent a local outbreak of RVF in China.

RVFV isolation and culture identification

Solution
were done in biosafety lab of Guangdong
Inspection and Quarantine Technology
Center. BGI laboratory performed
high-throughput sequencing of the
sample to gather genomic information
about RVFV. Analysis server of bioinformatics

Virus classification
Alignment of the full genome sequence of
Result
the RVFV isolate (named RVFV-Beijing
raw data Subtype identification
strain) revealed 100% identity of three
gene segments and 98% homologous to
Genomic assembly
RVFV Kakamas isolate in South Africa.

Evolutionary Site polymorphism Key site

analysis distribution analysis

Genetic variation analysis

Paper published on VIROLOGICA SINICA in June 2017

18

Case 5 Diagnosis of animal disease

Overview A group of goats, infected with unknown pathogens developed scabby lesions around their lips, muzzle, and
in their mouth. To efficiently control the unknown infection, throat swab samples from the affected goats
were tested using MGI Pathogen Fast Identification system with a report generated within two days.

The throat swab samples from goats were processed

Solution
using the MGI Pathogen Fast Identification system with
automatic DNA and RNA sample extraction. Analysis server of bioinformatics

A large proportion of sequencing reads in both DNA

Result
(64.2%) and RNA (44%) samples mapped directly to the
Orf virus which associates closely with the clinical
symptoms presented.

Table 1 The microorganism identification of DNA and RNA sample from goat swab

DNA RNA
Rank name of pathogen
reads number relative abundance reads number relative abundance

1 Orf_virus 358593 64.20% 11311 44%

2 Pseudocowpox_ virus 26658 4.80% 650 2.50%

3 Bacillus_subtilis 3130 0.60% 518 2.00%

4 Pseudomonas_aeruginosa 2011 0.40% 217 0.80%

5 Staphylococcus_aureus 1158 0.20% 220 0.90%

Direct comparison of the obtained sequencing reads to reference genome of Orf virus genome
showed 86.7% identity, 87.6% average coverage and 200X depth. (see Figure below)

Kb For ward Reverse

800
100

Sequencing depth frequence

0.8
600
75

Coverage

0.6
50 400

0.4
25 200

0.2
0
ref|NC_005336.1| 0 100 200 300 400

0.0
0 25 50 75 100 125 Sequencing depth(X)
Or f_virus
Fig.1 Alignment linear graph of Fig.2 Average coverage of viral genome Fig.3 Average sequencing depth of viral genome
assembled sequence and viral genome

To verify the result, a traditional PCR assay was then performed and showed positive confirmation of Orf virus.
The MGI sequencing technology is a highly accurate method for pathogen identification which aids in rapid diagnosis and
treatment of animal disease.
 Innovate Life Technology

Microbial Detection
Total Solution
MGI sequencing platform
for pathogen fast identification

MGI Tech Co., Ltd.

Service & Support

MGI has accumulated rich experience in gene sequencing with an excellent team of scientists and
engineers, who are committed to providing comprehensive technical support in each section: from
the installation, testing and operation, training, maintenance to subsequent upgrades, as well as the
laboratory system construction, experiment scheme design and sequencing data analysis. You will
experience an unprecedented journey of sequencing.

Contact Us
Address.: Building 11, Beishan Industrial Zone, Yantian District, Shenzhen, China 518083
Email: MGI-service@genomics.cn
Website: en.mgitech.cn
Tel: 4000-966-988
LinkedIn: www.linkedin.com/company/mgi-bgi
Twitter: @MGI_BGI

For Research Use Only

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Tech Co., Ltd. and their respective producers.

Version：2018.10

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